This document discusses hypertension and its treatment. It begins by defining hypertension and describing the types. It then discusses the normal blood pressure regulation system and how this is disrupted in hypertension. The remainder of the document focuses on the treatment of hypertension, describing various classes of antihypertensive drugs including diuretics, ACE inhibitors, angiotensin receptor blockers, calcium channel blockers, beta blockers, and others. It provides details on specific drugs in each class, their mechanisms of action, uses, and side effects.
This document discusses hypertension and its treatment. It defines hypertension as a blood pressure higher than 140/90 mmHg. It describes the types of hypertension and risk factors like stress, sodium intake, obesity, and smoking. Treatment is important to prevent damage to blood vessels and organs. Antihypertensive drugs lower blood pressure by interfering with normal blood pressure regulating mechanisms like the renin-angiotensin system and sympathetic nervous system. Common antihypertensive classes discussed include diuretics, ACE inhibitors, calcium channel blockers, and beta blockers.
This document discusses hypertension and its treatment. It defines hypertension and describes the types as essential or secondary. It explains how factors like stress, sodium intake, obesity, and smoking can cause environmental hypertension. The document outlines the need for treatment to prevent damage to blood vessels and organs. It then details various classes of antihypertensive drugs like diuretics, ACE inhibitors, calcium channel blockers, and others. It focuses on the renin-angiotensin system and how ACE inhibitors work to inhibit angiotensin II production and lower blood pressure.
Hypertension, or high blood pressure, is a disorder where blood pressure is consistently above 140/90 mmHg. It can be caused by unknown factors (essential hypertension) or other diseases (secondary hypertension). Untreated hypertension can damage blood vessels and organs over time.
The document discusses various types of medications used to treat hypertension, including diuretics, ACE inhibitors, angiotensin receptor blockers, calcium channel blockers, beta blockers, and alpha blockers. It provides details on specific drugs, their mechanisms of action, effects, uses, and potential side effects in the treatment of hypertension.
This document discusses types of hypertension, treatment of hypertension, and antihypertensive drugs. It describes the two main types of hypertension as essential and secondary. Treatment is necessary to prevent damage to blood vessels and the heart from high blood pressure. Several classes of antihypertensive drugs are discussed in detail, including diuretics, ACE inhibitors, angiotensin receptor blockers, calcium channel blockers, beta blockers, and others. The mechanisms of action and important effects of specific drugs like captopril, enalapril, lisinopril, and losartan are summarized as well.
This document discusses hypertension and antihypertensive drugs. It defines hypertension as a systolic blood pressure of 140 mmHg or higher and/or a diastolic blood pressure of 90 mmHg or higher. It describes the various classes of antihypertensive drugs including ACE inhibitors, angiotensin receptor blockers, calcium channel blockers, beta blockers, and diuretics. The mechanisms of action and side effects of these drug classes are explained in detail.
The document discusses the heart and hypertension. It defines normal blood pressure and describes the types and causes of hypertension. Hypertension usually has no symptoms, but can sometimes cause headaches, confusion or vision changes. Untreated hypertension can damage blood vessels and the heart over time, so treatment is important even in asymptomatic cases. Treatment includes diuretics, ACE inhibitors, calcium channel blockers, and other drugs that work to lower blood pressure by various mechanisms.
This document discusses various classes of drugs used to treat hypertension. It describes the mechanisms of action, effects, and examples of drugs in the following classes: diuretics, ACE inhibitors, angiotensin receptor blockers, beta blockers, calcium channel blockers, and vasodilators. It also provides background on renin-angiotensin system and the physiological role of angiotensin-converting enzyme. Specific drugs discussed in detail include captopril, enalapril, losartan, and metoprolol.
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This document discusses hypertension and its treatment with antihypertensive drugs. It defines hypertension and describes the types of hypertension. It explains the need to treat hypertension to prevent target organ damage like eye, brain, kidney and heart disease. It then discusses the normal blood pressure regulation mechanisms involving the heart, blood vessels, kidneys, baroreflex and renin-angiotensin system. The rest of the document summarizes the mechanisms, uses, and side effects of major classes of antihypertensive drugs like diuretics, beta-blockers, calcium channel blockers, ACE inhibitors, and angiotensin receptor blockers. It emphasizes that these drugs work by interfering with the normal blood pressure regulating mechanisms.
This document discusses various classes of antihypertensive drugs including diuretics, ACE inhibitors, angiotensin receptor blockers, calcium channel blockers, and alpha blockers. It provides details on specific drugs in each class, their mechanisms of action, effects, uses, and side effects. Thiazide diuretics like hydrochlorothiazide are recommended as first-line treatment for hypertension when used at low doses to avoid side effects. ACE inhibitors like lisinopril and enalapril are also good first-line options as they lower blood pressure without affecting electrolytes and have additional cardiovascular benefits. Angiotensin receptor blockers such as losartan are an alternative that provide complete blockade
This document discusses various classes of antihypertensive drugs including beta blockers, ACE inhibitors, calcium channel blockers, and diuretics. It explains their mechanisms of action in lowering blood pressure by reducing cardiac output, peripheral resistance, or sodium retention. Some advantages and side effects are provided for each drug class. The renin-angiotensin-aldosterone system and its role in blood pressure regulation is also summarized.
This document discusses antihypertensive drugs. It begins by defining hypertension and describing the types and outcomes of hypertension. It then covers the normal blood pressure regulation mechanisms. The document classifies antihypertensive drugs into several categories including diuretics, ACE inhibitors, angiotensin receptor blockers, calcium channel blockers, beta blockers, and others. For each drug class, it provides examples, discusses the mechanism of action, desirable properties, and drawbacks. It concludes by discussing the current treatment approaches and guidelines for selecting antihypertensive drugs.
This document discusses antihypertensive drugs. It begins by defining hypertension and describing the types and outcomes of hypertension. It then covers the normal blood pressure regulation mechanisms. The document classifies antihypertensive drugs into several categories including diuretics, ACE inhibitors, angiotensin receptor blockers, calcium channel blockers, beta blockers, and others. For each drug class, it provides examples, discusses the mechanism of action, desirable properties, and drawbacks. It concludes by discussing the current treatment approaches and guidelines for selecting antihypertensive drugs.
Hypertension is defined as a systolic blood pressure above 140 mmHg or a diastolic blood pressure above 90 mmHg. It can be essential (of unknown cause) or secondary to other diseases. Normal blood pressure is regulated by the kidney which controls blood volume via the renin-angiotensin-aldosterone system (RAAS). RAAS is activated when blood pressure or sodium levels drop, causing vasoconstriction and sodium retention. Antihypertensive drugs target different parts of this system, like ACE inhibitors which block the conversion of angiotensin I to angiotensin II, reducing peripheral resistance and blood volume. Captopril is an ACE inhibitor that lowers blood pressure by
This document summarizes the pharmacology of medications used to treat hypertension, including ACE inhibitors, ARBs, and CCBs. It reviews their mechanisms of action, efficacy, and safety profiles. It also discusses the renin-angiotensin system and its role in hypertension, current treatment guidelines, lifestyle modifications, and algorithms for antihypertensive drug selection and combination therapy.
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4. Types of
Hypertension
Essential Secondary
A disorder of unknown origin affecting the
Blood Pressure regulating mechanisms
Secondary to other disease processes
Environmental
Factors
Stress Na+ Intake Obesity Smoking
****************************************************
5. Treatment – Why?
Symptomatic treatment is Mandatory:
Damage to the vascular epithelium, paving the
path for atherosclerosis (IHD, CVA) or
nephropathy due to high intra-glomerular
pressure
Increased load on heart due to high BP can
cause CHF
Hypertension, even asymptomatic needs
treatment
6. Normal Blood Pressure Regulation
Hydraulic equation:
Blood Pressure = Cardiac output (CO) X
Resistance to passage of blood
through precapillary arterioles (PVR)
Physiologically CO and PVR is
maintained minute to minute by –
arterioles (1) postcapillary venules (2)
and Heart (3)
Kidney is the fourth site – volume of
intravascular fluid
Baroreflex, humoral mechanism and
renin-angiotensin- aldosterone system
regulates the above 4 sites
Local agents like Nitric oxide
In hypertensives – Baroreflex and
renal blood-volume control system –
set at higher level
All antihypertensives act via
interfering with normal mechanisms
8. The Renal response
Long-term blood pressure control – by controlling
blood volume
Reduction in renal pressure - intrarenal redistribution
of pressure and increased absorption of salt and
water
Decreased pressure in renal arterioles and
sympathetic activity – renin production – angiotensin
II production
Angiotensin II:
Causes direct constriction of renal arterioles
Stimulation of aldosterone synthesis – sodium
absorption and increase in intravascular blood volume
9. Antihypertensive Drugs
Diuretics:
Thiazides: Hydrochlorothiazide, chlorthalidone
High ceiling: Furosemide
K+ sparing: Spironolactone, triamterene and amiloride
MOA: Acts on Kidneys to increase excretion of Na and H2O –
decrease in blood volume – decreased BP
Angiotensin-converting Enzyme (ACE) inhibitors:
Captopril, lisinopril., enalapril, ramipril and fosinopril
MOA: Inhibit synthesis of Angiotensin II – decrease in peripheral
resistance and blood volume
Angiotensin (AT1) blockers:
Losartan, candesartan, valsartan and telmisartan
MOA: Blocks binding of Angiotensin II to its receptors
10. Antihypertensive Drugs
Centrally acting:
Clonidine, methyldopa
MOA: Act on central α2A receptors to decrease sympathetic
outflow – fall in BP
ß-adrenergic blockers:
Non selective: Propranolol (others: nadolol, timolol, pindolol,
labetolol)
Cardioselective: Metoprolol (others: atenolol, esmolol,
betaxolol)
MOA: Bind to beta adrenergic receptors and blocks the activity
ß and α – adrenergic blockers:
Labetolol and carvedilol
α – adrenergic blockers:
Prazosin, terazosin, doxazosin, phenoxybenzamine and
phentolamine
MOA: Blocking of alpha adrenergic receptors in smooth muscles -
vasodilatation
11. Antihypertensive Drugs –
Calcium Channel Blockers (CCB):
Verapamil, diltiazem, nifedipine, felodipine, amlodipine,
nimodipine etc.
MOA: Blocks influx of Ca++ in smooth muscle cells –
relaxation of SMCs – decrease BP
K+ Channel activators:
Diazoxide, minoxidil, pinacidil and nicorandil
MOA: Leaking of K+ due to opening – hyper polarization
of SMCs – relaxation of SMCs
Vasodilators:
Arteriolar – Hydralazine (also CCBs and K+ channel
activators)
Arterio-venular: Sodium Nitroprusside
12. Diuretics
Drugs causing net loss of Na+ and water in urine
Mechanism of antihypertensive action:
Initially: diuresis – depletion of Na+ and body fluid
volume – decrease in cardiac output
Subsequently after 4 - 6 weeks, Na+ balance and CO
is regained by 95%, but BP remains low!
Q: Why? Answer: reduction in total peripheral
resistance (TPR) due to deficit of little amount of Na+
and water (Na+ causes vascular stiffness)
Similar effect is seen with sodium restriction (low
sodium diet)
13. Thiazide diuretics – adverse effects
Adverse Effects:
Hypokalaemia – muscle pain and fatigue
Hyperglycemia: Inhibition of insulin release due to K+
depletion (proinsulin to insulin) – precipitation of
diabetes
Hyperlipidemia: rise in total LDL level – risk of stroke
Hyperurecaemia: inhibition of urate excretion
Sudden cardiac death – tosades de pointes
(hypokalaemia)
All the above metabolic side effects – higher doses (50
– 100 mg per day)
But, its observed that these adverse effects are
minimal with low doses (12.5 to 25 mg) - Average fall
in BP is 10 mm of Hg
14. Thiazide diuretics – current status
Effects of low dose:
No significant hypokalaemia
Low incidence of arrhythmia
Lower incidence of hyperglycaemia, hyperlipidemia and
hyperuricaemia
Reduction in MI incidence
Reduction in mortality and morbidity
JNC recommendation:
JNC recommends low dose of thiazide therapy (12.5 – 25
mg per day) in essential hypertension
Preferably should be used with a potassium sparing diuretic
as first choice in elderly
If therapy fails – another antihypertensive but do not
increase the thiazide dose
Loop diuretics are to be given when there is severe
hypertension with retention of body fluids
15. Diuretics
K+ sparing diuretics:
Thiazide and K sparing diuretics are combined
therapeutically – DITIDE (triamterene + benzthiazide)
is popular one
Modified thiazide: indapamide
Indole derivative and long duration of action (18 Hrs) –
orally 2.5 mg dose
It is a lipid neutral i.e. does not alter blood lipid
concentration, but other adverse effects may remain
Loop diuretics:
Na+ deficient state is temporary, not maintained round
–the-clock and t.p.r not reduced
Used only in complicated cases – CRF, CHF marked
fluid retention cases
17. RAS - Introduction
Renin is a proteolytic enzyme and also called
angiotensinogenase
It is produced by juxtaglomerular cells of kidney
It is secreted in response to:
Decrease in arterial blood pressure
Decrease Na+ in macula densa
Increased sympathetic nervous activity
Renin acts on a plasma protein – Angiotensinogen (a
glycoprotein synthesized and secreted into the bloodstream by
the liver) and cleaves to produce a decapeptide Angiotensin-I
Angiotensin-I is rapidly converted to Angiotensin-II (octapeptide)
by ACE (present in luminal surface of vascular endothelium)
Furthermore degradation of Angiotensin-II by peptidases
produce Angiotensin-III
Both Angiotensin-II and Angiotensin-III stimulates Aldosterone
secretion from Adrenal Cortex (equipotent)
AT-II has very short half life – 1 min
19. RAS – actions of Angiotensin-II.
1. Powerful vasoconstrictor particularly arteriolar – direct action and
release of Adr/NA release
Promotes movement of fluid from vascular to extravascular
More potent vasopressor agent than NA – promotes Na+ and water
reabsorption
It increases myocardial force of contraction (CA++ influx promotion)
and increases heart rate by sympathetic activity, but reflex
bradycardia occurs
Cardiac output is reduced and cardiac work increases
2. Aldosterone secretion stimulation – retention of Na++ in body
3. Vasoconstriction of renal arterioles – rise in IGP – glomerular damage
4. Decreases NO release
5. Decreases Fibrinolysis in blood
6. Induces drinking behaviour and ADH release by acting in CNS –
increase thirst
7. Mitogenic effect – cell proliferation
20. Angiotensin-II
What are the ill effects on chronic ?
Volume overload and increased t.p.r
Cardiac hypertrophy and remodeling
Coronary vascular damage and remodeling
Hypertension – long standing will cause ventricular
hypertrophy
Myocardial infarction – hypertrophy of non-infarcted
area of ventricles
Renal damage
Risk of increased CVS related morbidity and mortality
ACE inhibitors reverse cardiac and vascular
hypertrophy and remodeling
21. Angiotensin-II – Pathophysiological
Roles
1. Mineraocorticoid secretion
2. Electrolyte, blood volume and pressure homeostasis: Renin is
released when there is changes in blood volume or pressure
or decreased Na+ content
Intrarenal baroreceptor pathway – reduce tension in the afferent
glomerular arterioles by local production of Prostaglandin –
intrarenal regulator of blood flow and reabsorption
Low Na+ conc. in tubular fluid – macula densa pathway – COX-2
and nNOS are induced – release of PGE2 and PGI2 – more renin
release
Baroreceptor stimulation increases sympathetic impulse – via
beta-1 pathway – renin release
Renin release – increased Angiotensin II production –
vasoconstriction and increased Na+ and water reabsorption
Long term stabilization of BP is achieved – long-loop negative
feedback and short-loop negative feedback mechanism
3. Hypertension
4. Secondary hyperaldosteronism
23. ACE inhibitors in Hypertension
Captopril
Sulfhydryl containing dipeptide and abolishes
pressor action of Angiotensin-I and not
Angiotensin-II and does not block AT
receptors
Pharmacokinetics:
Available only orally, 70% - 75% is absorbed
Partly absorbed and partly excreted
unchanged in urine
Food interferes with its absorption
Half life: 2 Hrs, but action stays for 6-12 Hrs
24. Captopril – Pharmacological actions
1. In Normal:
Depends on Na+ status – lowers BP marginally on single dose
When Na+ depletion – marked lowering of BP
2. In hypertensive:
Lowers PVR and thereby mean, systolic and diastolic BP
RAS is overactive in 80% of hypertensive cases and contributes
to the maintenance of vascular tone – inhibition causes lowering
of BP
Initially correlates with renin-angiotensin status but chronic
administration is independent of renin activity
Captopril decreases t.p.r on long term – arterioles dilate – fall in
systolic and diastolic BP
No effect on Cardiac output
Postural hypotension is not a problem - reflex sympathetic
stimulation does not occur
Renal blood flow is maintained – greater dilatation of vessels
25. Captopril – Adverse effects
Cough – persistent brassy cough in 20% cases – inhibition of
bradykinin and substanceP breakdown in lungs
Hyperkalemia in renal failure patients with K+ sparing diuretics,
NSAID and beta blockers (routine check of K+ level)
Hypotension – sharp fall may occur – 1st dose
Acute renal failure: CHF and bilateral renal artery stenosis
Angioedema: swelling of lips, mouth, nose etc.
Rashes, urticaria etc
Dysgeusia: loss or alteration of taste
Foetopathic: hypoplasia of organs, growth retardation etc
Neutripenia
Contraindications: Pregnancy, bilateral renal artery stenosis,
hypersensitivity and hyperkalaemia
26. ACE inhibitors - Enalapril
It’s a prodrug – converted to enalaprilate
Advantages over captopril:
Longer half life – OD (5-20 mg OD)
Absorption not affected by food
Rash and loss of taste are less frequent
Longer onset of action
Less side effects
27. ACE inhibitors – Ramipril
It’s a popular ACEI now
It is also a prodrug with long half life
Tissue specific – Protective of heart and
kidney
Uses: Diabetes with hypertension, CHF, AMI
and cardio protective in angina pectoris
Blacks in USA are resistant to Ramipril –
addition of diuretics help
Dose: Start with low dose; 2.5 to 10 mg daily
28. ACE inhibitors – Lisinopril
It’s a lysine derivative
Not a prodrug
Slow oral absorption – less chance of 1st
dose phenomenon
Absorption not affected by food and not
metabolized – excrete unchanged in urine
Long duration of action – single daily dose
Doses: available as 1.25, 2.5, 5, 10 1nd 20
mg tab – start with low dose
29. ACE inhibitors and hypertension
1st line of Drug:
No postural hypotension or electrolyte imbalance (no
fatigue or weakness)
Safe in asthmatics and diabetics
Prevention of secondary hyperaldosteronism and K+
loss
Renal perfusion well maintained
Reverse the ventricular hypertrophy and increase in
lumen size of vessel
No hyperuraecemia or deleterious effect on plasma
lipid profile
No rebound hypertension
Minimal worsening of quality of life – general wellbeing,
sleep and work performance etc.
30. ACE inhibitors – other uses
Hypertension
Congestive Heart Failure
Myocardial Infarction
Prophylaxis of high CVS risk subjects
Diabetic Nephropathy
Schleroderma crisis
31. Angiotensin Receptor Blockers
(ARBs) -
Angiotensin Receptors:
Specific angiotensin receptors have been discovered, grouped
and abbreviated as – AT1 and AT2
They are present on the surface of the target cells
Most of the physiological actions of angiotensin are mediated
via AT1 receptor
Transducer mechanisms of AT1 inhibitors: In different tissues
show different mechanisms. For example -
PhospholipaseC-IP3/DAG-intracellular Ca++ release
mechanism – vascular and visceral smooth muscle
contraction
In myocardium and vascular smooth muscles AT1 receptor
mediates long term effects by MAP kinase and others
Losartan is the specific AT1 blocker
32. Angiotensin Receptor Blockers
(ARBs) - Losartan
Competitive antagonist and inverse agonist of
AT1 receptor
Does not interfere with other receptors except
TXA2
Blocks all the actions of A-II -
vasoconstriction, sympathetic stimulation,
aldosterone release and renal actions of salt
and water reabsorption
No inhibition of ACE
33. Losartan
Theoretical superiority over ACEIs:
Cough is rare – no interference with bradykinin and other
ACE substrates
Complete inhibition of AT1 – alternative remains with ACEs
Result in indirect activation of AT2 – vasodilatation
(additional benefit)
Clinical benefit of ARBs over ACEIs – not known
However, losartan decreases BP in hypertensive which is for
long period (24 Hrs)
heart rate remains unchanged and cvs reflxes are not
interfered
no significant effect in plasma lipid profile, insulin sensitivity
and carbohydrate tolerance etc
Mild uricosuric effect
34. Losartan
Pharmacokinetic:
Absorption not affected by food but unlike ACEIs its
bioavailability is low
High first pass metabolism
Carboxylated to active metabolite E3174
Highly bound to plasma protein
Do not enter brain
Adverse effects:
Foetopathic like ACEIs – not to be administered in
pregnancy
Rare 1st dose effect hypotension
Low dysgeusia and dry cough
Lower incidence of angioedema
Available as 25 and 50 mg tablets
35. Beta-adrenergic blockers
Non selective: Propranolol (others: nadolol, timolol, pindolol,
labetolol)
Cardioselective: Metoprolol (others: atenolol, esmolol,
betaxolol)
All beta-blockers similar antihypertensive effects – irrespective of
additional properties
Reduction in CO but no change in BP initially but slowly
Adaptation by resistance vessels to chronically reduced CO –
antihypertensive action
Other mechanisms – decreased renin release from kidney (beta-1
mediated)
Reduced NA release and central sympathetic outflow reduction
Non-selective ones – reduction in g.f.r but not with selective ones
Drugs with intrinsic sympathomimetic activity may cause less
reduction in HR and CO
36. Beta-adrenergic blockers
Advantages:
No postural hypotension
No salt and water retention
Low incidence of side effects
Low cost
Once a day regime
Preferred in young non-obese patients, prevention of sudden
cardiac death in post infarction patients and progression of
CHF
Drawbacks (side effects):
Fatigue, lethargy (low CO?) – decreased work capacity
Loss of libido – impotence
Cognitive defects – forgetfulness
Difficult to stop suddenly
Therefore cardio-selective drugs are preferred now
37. Beta-adrenergic blockers
Advantages of cardio-selective over non-selective:
In asthma
In diabetes mellitus
In peripheral vascular disease
Current status:
JNC 7 recommends - 1st line of antihypertensive along
with diuretics and ACEIs
Preferred in young non-obese hypertensive
Angina pectoris and post angina patients
Post MI patients – useful in preventing mortality
In old persons, carvedilol – vasodilatory action can be
given
38. Αlpha-adrenergic blockers
Non selective alpha blockers are not used in chronic
essential hypertension (phenoxybenzamine,
phentolamine), only used sometimes as in
phaechromocytoma
Specific alpha-1 blockers like prazosin, terazosin and
doxazosine are used
PRAZOSIN is the prototype of the alpha-blockers
Reduction in t.p.r and mean BP – also reduction in
venomotor tone and pooling of blood – reduction in
CO
Does not produce tachycardia as presynaptic auto
(alpha-2) receptors are not inhibited – autoregulation
of NA release remains intact
39. Αlpha-adrenergic blockers.
Adverse effects:
Prazosin causes postural hypotension – start 0.5 mg at bed
time with increasing dose and upto 10 mg daily
Fluid retention in monotherapy
Headache, dry mouth, weakness, dry mouth, blurred vision,
rash, drowsiness and failure of ejaculation in males
Current status:
Several advantages – improvement of carbohydrate
metabolism – diabetics, lowers LDL and increases HDL,
symptomatic improvement in BHP
But not used as first line agent, used in addition with other
conventional drugs which are failing – diuretic or beta
blocker
Doses: Available as 0.5 mg, 1 mg, 2.5 mg, 5 mg etc. dose:1-4
mg thrice daily (Minipress/Prazopress)
41. Calcium Channel Blockers –
Mechanism of action
Three types Ca+ channels in smooth muscles – Voltage
sensitive, receptor operated and leak channel
Voltage sensitive are again 3 types – L-Type, T-Type and N-
Type
Normally, L-Type of channels admit Ca+ and causes
depolarization – excitation-contraction coupling through
phosphorylation of myosin light chain – contraction of vascular
smooth muscle – elevation of BP
CCBs block L-Type channel:
Smooth Muscle relaxation
Negative chronotropic, ionotropic and chronotropic effects in heart
DHPs have highest smooth muscle relaxation and vasodilator
action followed by verapamil and diltiazem
Other actions: DHPs have diuretic action
42. Calcium Channel Blockers
Advantages:
Unlike diuretics no adverse metabolic effects but
mild adverse effects like – dizziness, fatigue etc.
Do not compromise haemodynamics – no
impairment of work capacity
No sedation or CNS effect
Can be given to asthma, angina and PVD patients
No renal and male sexual function impairment
No adverse fetal effects and can be given in
pregnancy
Minimal effect on quality of life
43. Calcium Channel Blockers –
current status
As per JNC 7 CCBs are not 1st line of
antihypertensive unless indicated –
ACEI/diuretics/beta blockers
However its been used as 1st line by many because
of excellent tolerability and high efficacy
Preferred in elderly and prevents stroke
CCBs are effective in low Renin hypertension
They are next to ACE inhibitors in inhibition of
albuminuria and prevention of diabetic nephropathy
Immediate acting Nifedipine is not encouraged
anymore
44. Calcium Channel Blockers
Contraindications:
Unstable angina
Heart failure
Hypotension
Post infarct cases
Severe aortic stenosis
Preparation and dosage:
Amlodipine – 2.5, 5 and 10 mg tablets (5-10 mg
OD) – Stamlo, Amlopres, Amlopin etc.
Nimodipine – 30 mg tab and 10 mg/50 ml injection
– Vasotop, Nimodip, Nimotide etc.
45. Vasodilators - Hydralazine
Directly acting vasodilator
MOA: hydralazine molecules combine with receptors in the
endothelium of arterioles – NO release – relaxation of vascular smooth
muscle – fall in BP
Subsequenly fall in BP – stimulation of adrenergic system leading to
Cardiac stimulation producing palpitation and rise in CO even in
IHD and patients – anginal attack
Tachycardia
Increased Renin secretion – Na+ retention
These effects are countered by administration of beta blockers and
diuretics
However many do not agree to this theory
Uses: 1) Moderate hypertension when 1st line fails – with beta-blockers
and diuretics 2) Hypertension in Pregnancy, Dose 25-50 mg OD
46. Vasodilators - Minoxidil
Powerful vasodilator, mainly 2 major uses – antihypertensive
and alopecia
Prodrug and converted to an active metabolite which acts by
hyperpolarization of smooth muscles and thereby relaxation of
SM – leading to hydralazine like effects
Rarely indicated in hypertension especially in life threatening
ones
More often in alopecia to promote hair growth
Orally not used any more
Topically as 2-5% lotion/gel and takes months to get effects
MOA of hair growth:
Enhanced microcirculation around hair follicles and also by direct
stimulation of follicles
Alteration of androgen effect of hair follicles
47. Sodium Nitroprusside
Rapidly and consistently acting vasodilator
Relaxes both resistance and capacitance vessels and reduces
t.p.r and CO (decrease in venous return)
Unlike hydralazine it produces decrease in cardiac work and no
reflex tachycardia.
Improves ventricular function in heart failure by reducing preload
MOA: RBCs convert nitroprusside to NO – relaxation also by
non-enzymatically to NO by glutathione
Uses: Hypertensive Emergencies, 50 mg is added to 500 ml of
saline/glucose and infused slowly with 0.02 mg/min initially and
later on titrated with response (wrap with black paper)
Adverse effects: All are due release of cyanides (thiocyanate) –
palpitation, pain abdomen, disorientation, psychosis, weakness
and lactic acidosis.
48. Centrally acting Drugs
Alpha-Methyldopa: a prodrug
Precursor of Dopamine and NA
MOA: Converted to alpha methyl noradrenaline which acts
on alpha-2 receptors in brain and causes inhibition of
adrenergic discharge in medulla – fall in PVR and fall in BP
Various adverse effects – cognitive impairement, postural
hypotension, positive coomb`s test etc. – Not used
therapeutically now except in Hypertension during
pregnancy
Clonidine: Imidazoline derivative, partial agonist of central
alpha-2 receptor
Not frequently used now because of tolerance and
withdrawal hypertension
Read it yourself
50. Treatment of Hypertension: 7
classification
Categories
BP Systolic Diastolic
Normal >120 <80
Prehypertension 120-139 80-89
Stage1 149-159 90-99
Stage2 >160 >100
Risk factors
1. Age above 55 and 65 in
Men and Woman
respectively
2. Family History
3. Smoking
4. DM and Dyslipidemia
5. Hypertension
6. Obesity
7. Microalbuminuria
53. Treatment of Hypertension – General
principles
Stage I:
Start with a single most appropriate drug with a low
dose. Preferably start with Thiazides. Others like beta-
blockers, CCBs, ARBs and ACE inhibitors may also be
considered. CCB – in case of elderly and stroke
prevention. If required increase the dose moderately
Partial response or no response – add from another
group of drug, but remember it should be a low dose
combination
If not controlled – change to another low dose
combination
In case of side effects lower the dose or substitute with
other group
Stage 2: Start with 2 drug combination – one should
be diuretic
54. Treatment of Hypertension –
combination therapy
In clinical practice a large number of patients require
combination therapy – the combination should be
rational and from different patterns of haemodynamic
effects
Sympathetic inhibitors (not beta-blockers) and
vasodilators + diuretics
Diuretics, CCBs, ACE inhibitors and vasodilators +
beta blockers (blocks renin release)
Hydralazine and CCBs + beta-blockers (tachycardia
countered)
ACE inhibitors + diuretics
3 (three) Drug combinations:
CCB+ACE/ARB+diuretic; CCB+Beta blocker+
diuretic; ACEI/ARB+ beta blocker+diuretic
55. Treatment of Hypertension.
Never combine:
Alpha or beta blocker and clonidine - antagonism
Nifedepine and diuretic synergism
Hydralazine with DHP or prazosin – same type of
action
Diltiazem and verapamil with beta blocker –
bradycardia
Methyldopa and clonidine
Hypertension and pregnancy:
No drug is safe in pregnancy
Avoid diuretics, propranolol, ACE inhibitors, Sodium
nitroprusside etc
Safer drugs: Hydralazine, Methyldopa, cardioselective
beta blockers and prazosin
56. Hypertensive Emergencies
Cerebrovascular accident or head injury with high BP
Left ventricular failure with pulmonary edema due to
hypertension
Hypertensive encephalopathy
Angina or MI with raised BP
Acute renal failure with high BP
Eclampsia
Pheochromocytoma, cheese reaction and clonidine withdrawal
Drugs:
Sodium Nitroprusside (20-300 mcg/min) – dose titration and
monitoring
GTN (5-20 mcg/min) – cardiac surgery, LVF, MI and angina
Esmolol (0.5 mg/kg bolus) and 50-200mcg/kg/min - useful in
reducing cardiac work
Phentolamine – pheochromocytoma, cheese reaction nd clonidine
withdrawal (5-10 mg IV)
57. Desirable to know/learn
Classification of Antihypertensive
Antihypertensive mechanisms: Diuretics, ACE
inhibitors, ARBs, Beta-blockers, alpha-blockers,
CCBs, Vasodilators and central sympatholytics
Present status of above mentioned group of Drugs
Common Adverse effects of above groups of Drugs
Pharmacotherapy of Hypertension
Pharmacotherapy of hypertensive emergencies
Preparation and dosage of commonly used drugs of
above mentioned groups